NT5C2

Summary

NT5C2 (5’-nucleotidase, cytosolic II, HGNC:8022) is a protein-coding gene on chromosome 10q24.32-q24.33, encoding Cytosolic purine 5’-nucleotidase (P49902). Broad specificity cytosolic 5’-nucleotidase that catalyzes the dephosphorylation of 6-hydroxypurine nucleoside 5’-monophosphates. In precision oncology, NT5C2 R367Q is associated with resistance to Mercaptopurine + Thioguanine in Childhood Acute Lymphocytic Leukemia (CIViC Level C); 13 further curated variant–drug associations are listed below.

This gene encodes a hydrolase that serves as an important role in cellular purine metabolism by acting primarily on inosine 5’-monophosphate and other purine nucleotides.

Source: NCBI Gene 22978 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex hereditary spastic paraplegia (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 97
• Clinical variants (ClinVar): 260 total — 19 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 33
• Druggable target: yes
• Precision-oncology evidence (CIViC): 14 curated variant–drug associations
• MANE Select transcript: NM_001351169

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8022
Approved symbol	NT5C2
Name	5’-nucleotidase, cytosolic II
Location	10q24.32-q24.33
Locus type	gene with protein product
Status	Approved
Aliases	PNT5, GMP, cN-II, SPG65
Ensembl gene	ENSG00000076685
Ensembl biotype	protein_coding
OMIM	600417
Entrez	22978

Gene structure

Transcript identifiers

Ensembl transcripts: 62 — 45 protein_coding, 10 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000343289, ENST00000369857, ENST00000404739, ENST00000421281, ENST00000452156, ENST00000458345, ENST00000461461, ENST00000467380, ENST00000469228, ENST00000470228, ENST00000470299, ENST00000481549, ENST00000487810, ENST00000552185, ENST00000674696, ENST00000674728, ENST00000674860, ENST00000675020, ENST00000675040, ENST00000675164, ENST00000675326, ENST00000675436, ENST00000675645, ENST00000675811, ENST00000675985, ENST00000676428, ENST00000676449, ENST00000874297, ENST00000874298, ENST00000874299, ENST00000874300, ENST00000874301, ENST00000874302, ENST00000874303, ENST00000874304, ENST00000874305, ENST00000874306, ENST00000874307, ENST00000874308, ENST00000874309, ENST00000874310, ENST00000874311, ENST00000874312, ENST00000874313, ENST00000874314, ENST00000874315, ENST00000920535, ENST00000920536, ENST00000920537, ENST00000920538, ENST00000920539, ENST00000920540, ENST00000920541, ENST00000920542, ENST00000920543, ENST00000920544, ENST00000920545, ENST00000964133, ENST00000964134, ENST00000964135, ENST00000964136, ENST00000964137

RefSeq mRNA: 31 — MANE Select: NM_001351169 NM_001134373, NM_001351169, NM_001351170, NM_001351171, NM_001351172, NM_001351173, NM_001351174, NM_001351175, NM_001351176, NM_001351177, NM_001351178, NM_001351179, NM_001351180, NM_001351181, NM_001351182, NM_001351183, NM_001351184, NM_001351185, NM_001351186, NM_001351187, NM_001351188, NM_001351189, NM_001351190, NM_001351191, NM_001351192, NM_001351193, NM_001351194, NM_001351195, NM_001351196, NM_001351197, NM_012229

CCDS: CCDS7544, CCDS91339, CCDS91340

Canonical transcript exons

ENST00000404739 — 19 exons

Exon	Start	End
ENSE00001658312	103193236	103193272
ENSE00001945495	103088038	103089908
ENSE00003470626	103091564	103091615
ENSE00003472845	103090611	103090787
ENSE00003474155	103101045	103101102
ENSE00003479528	103099926	103100019
ENSE00003480950	103093972	103094038
ENSE00003486547	103139406	103139479
ENSE00003524653	103105706	103105801
ENSE00003533796	103101235	103101326
ENSE00003540965	103106589	103106706
ENSE00003557470	103174858	103174982
ENSE00003576701	103095939	103095980
ENSE00003602669	103090936	103090996
ENSE00003605538	103094348	103094455
ENSE00003633057	103093139	103093309
ENSE00003693615	103098931	103098984
ENSE00003790804	103097291	103097374
ENSE00003901306	103181185	103181328

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.5907 / max 540.0383, expressed in 1808 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
111217	27.9565	1808
111210	0.4349	163
111220	0.4144	173
111215	0.2793	162
111207	0.1751	61
111214	0.1704	106
111213	0.0766	28
111211	0.0760	24
111212	0.0075	1

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	98.74	gold quality
buccal mucosa cell	CL:0002336	98.17	gold quality
oral cavity	UBERON:0000167	98.07	gold quality
amniotic fluid	UBERON:0000173	97.68	gold quality
esophagus squamous epithelium	UBERON:0006920	97.59	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.47	gold quality
cervix squamous epithelium	UBERON:0006922	97.25	gold quality
trabecular bone tissue	UBERON:0002483	97.21	gold quality
pharyngeal mucosa	UBERON:0000355	97.09	gold quality
epithelium of esophagus	UBERON:0001976	97.05	gold quality
lower esophagus mucosa	UBERON:0035834	96.80	gold quality
right lobe of thyroid gland	UBERON:0001119	96.71	gold quality
thyroid gland	UBERON:0002046	96.57	gold quality
palpebral conjunctiva	UBERON:0001812	96.53	gold quality
left lobe of thyroid gland	UBERON:0001120	96.52	gold quality
gluteal muscle	UBERON:0002000	96.38	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.36	gold quality
saliva-secreting gland	UBERON:0001044	96.30	gold quality
esophagus mucosa	UBERON:0002469	96.29	gold quality
cortical plate	UBERON:0005343	96.23	gold quality
monocyte	CL:0000576	96.20	gold quality
biceps brachii	UBERON:0001507	96.10	gold quality
squamous epithelium	UBERON:0006914	96.08	gold quality
blood	UBERON:0000178	96.05	gold quality
mononuclear cell	CL:0000842	95.96	gold quality
ganglionic eminence	UBERON:0004023	95.91	gold quality
minor salivary gland	UBERON:0001830	95.90	gold quality
mouth mucosa	UBERON:0003729	95.86	gold quality
leukocyte	CL:0000738	95.77	gold quality
superior surface of tongue	UBERON:0007371	95.70	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.25

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

64 targeting NT5C2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-885-5P	99.59	68.59	879
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-409-3P	99.50	66.33	1192

Literature-anchored findings (GeneRIF, showing 38)

• cN-II has a role in protecting against progression of non-small cell lung cancer (PMID:15923058)
• the expression level of cN-II mRNA might be a prognostic factor of high-risk MDS. (PMID:17350683)
• Data describe the crystal structure of human cytosolic 5’-nucleotidase II and discuss its allosteric regulation and substrate recognition. (PMID:17405878)
• In leukoblasts from 82 patients with acute myeloid leukemia, various extent and frequency of differential allelic expression in the CDA, DCK, NT5C2, NT5C3, and TP53 genes was observed. (PMID:18775979)
• The DCK/cN-II ratio was again proportional to ara-CTP production and to ara-C sensitivity. (PMID:19428333)
• seven high-resolution structures of human cN-II, including a ligand-free form and complexes with various substrates and effectors, were presented. (PMID:21396942)
• Polymorphisms in the CYP17A1 and NT5C2 genes influence a reduction in both visceral and subcutaneous fat mass in Japanese women. (PMID:22071413)
• analysis of Drosophila and human 7-methyl GMP-specific nucleotidases (PMID:23223233)
• These results suggest that mutations in NT5C2 are associated with the outgrowth of drug-resistant clones in acute lymphoblastic leukemia (PMID:23377183)
• results highlight the prominent role of relapse-specific mutations in NT5C2 as a mechanism of resistance to 6-Mercaptopurine and a genetic driver of relapse in acute lymphoblastic leukemia (PMID:23377281)
• Four novel body mass index-associated loci near the KCNQ1(rs2237892), ALDH2/MYL2 (rs671, rs12229654), ITIH4 (rs2535633) and NT5C2 (rs11191580) genes are identified in East Asian-ancestry populations. (PMID:24861553)
• cN-II co-immunoprecipitated both with wild type Ipaf and its LRR domain after transfection with corresponding expression vectors, but not with Ipaf lacking the LRR domain. (PMID:25811392)
• Data indicate that type II cytosolic 5’-nucleotidase (cN-II) exerts a role in nucleotide and drug metabolism and regulating cell survival. (PMID:25857773)
• Leukemia Relapse-Associated Mutation of NT5C2 Gene is Rare in de Novo Acute Leukemias and Solid Tumors. (PMID:26259531)
• this study implicates altered neural expression of BORCS7, AS3MT, and NT5C2 in susceptibility to schizophrenia arising from genetic variation at the chromosome 10q24 locus (PMID:27004590)
• Using data from a large-scale genome-wide association study of schizophrenia, study identified several potentially functional variants relating to miRNA function with our top finding being a schizophrenia protective allele that disrupts miR-206s binding to NT5C2 thus leading to increased expression of this gene. (PMID:27424800)
• acute lymphoblastic leukemia-specific mutations affect regulation of cN-II (PMID:27756303)
• NT5C2 variant rs11191580 conferred susceptibility to schizophrenia and affected the clinical symptoms of schizophrenia in a South Chinese Han population. (PMID:27901213)
• The aberrantly spliced NT5C2 showed substantial reduction in expression level in the in-vitro study, indicating marked instability of the mutant NT5C2 protein. (PMID:28327087)
• NT5C2 mutations seem to have a broad clinical spectrum and should be sought in patients manifesting either as uncomplicated or complicated spastic paraplegia (PMID:28884889)
• intersubunit interaction forms structural basis of hyperactive NT5C2 in drug-resistant leukemia in which heterozygous NT5C2 mutation gave rise to hetero-tetramer mutant and WT proteins. (PMID:29535428)
• Results uncover dynamic mechanisms of enzyme regulation targeted by chemotherapy resistance-driving NT5C2 mutations in relapsed acute lymphoblastic leukemia. (PMID:29990496)
• Targeted sequencing of NT5C2 did not identify any missense variants associated with rs72846714 or wmEry-TGN/wmDNA-TG. (PMID:30201983)
• NT5C2 deletion in mice protects against high-fat diet-induced weight gain, adiposity, insulin resistance and associated hyperglycemia (PMID:30803894)
• We provide an extensive neurobiological characterization of the psychiatric risk gene NT5C2, describing its previously unknown role in the regulation of AMPK signaling and protein translation in neural stem cells and its association with Drosophila melanogaster motility behavior (PMID:31097295)
• NT5C2 mutations alter thiopurine metabolism and cellular disposition (PMID:31358663)
• Subclonal NT5C2 mutations are associated with poor outcomes after relapse of pediatric acute lymphoblastic leukemia. (PMID:31971569)
• NT5C2 Gene Polymorphisms and the Risk of Coronary Heart Disease. (PMID:32541135)
• Association between NT5C2 rs11191580 and autism spectrum disorder in the Chinese Han population. (PMID:32590138)
• Enhanced migration of breast and lung cancer cells deficient for cN-II and CD73 via COX-2/PGE2/AKT axis regulation. (PMID:32970317)
• NT5C2 methylation regulatory interplay between DNMT1 and insulin receptor in type 2 diabetes. (PMID:32999320)
• Effects of NT5C2 Germline Variants on 6-Mecaptopurine Metabolism in Children With Acute Lymphoblastic Leukemia. (PMID:33124053)
• CD73 and cN-II regulate the cellular response to chemotherapeutic and hypoxic stress in lung adenocarcinoma cells. (PMID:33434633)
• Cytosolic 5’-Nucleotidase II Silencing in Lung Tumor Cells Regulates Metabolism through Activation of the p53/AMPK Signaling Pathway. (PMID:34209768)
• NUDT15 polymorphism and NT5C2 and PRPS1 mutations influence thiopurine sensitivity in acute lymphoblastic leukaemia cells. (PMID:34636169)
• Associations between Gene-Gene Interaction and Overweight/Obesity of 12-Month-Old Chinese Infants. (PMID:35295960)
• Silencing of circ-NT5C2 retards the progression of IL-1beta-induced osteoarthritis in an in vitro cell model by targeting the miR-142-5p/NAMPT axis. (PMID:36540014)
• Schizophrenia risk proteins ZNF804A and NT5C2 interact in cortical neurons. (PMID:38279611)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nt5c2	ENSMUSG00000025041
rattus_norvegicus	Nt5c2	ENSRNOG00000020179
drosophila_melanogaster	Nt5c	FBGN0033426
drosophila_melanogaster	Nt5b	FBGN0052549
caenorhabditis_elegans		WBGENE00022201

Paralogs (4): NT5DC3 (ENSG00000111696), NT5DC4 (ENSG00000144130), NT5DC2 (ENSG00000168268), NT5DC1 (ENSG00000178425)

Protein

Protein identifiers

Cytosolic purine 5’-nucleotidase — P49902 (reviewed: P49902)

Alternative names: Cytosolic 5’-nucleotidase II, Cytosolic IMP/GMP-specific 5’-nucleotidase, Cytosolic nucleoside phosphotransferase 5’N, High Km 5’-nucleotidase

All UniProt accessions (12): P49902, A0A384MED8, A0A6Q8PEZ2, A0A6Q8PF50, A0A6Q8PFH2, A0A6Q8PG36, A0A6Q8PHB5, A0A6Q8PHP0, H0YHR8, Q5JUV6, S4R3A6, S4R3E7

UniProt curated annotations — full annotation on UniProt →

Function. Broad specificity cytosolic 5’-nucleotidase that catalyzes the dephosphorylation of 6-hydroxypurine nucleoside 5’-monophosphates. In addition, possesses a phosphotransferase activity by which it can transfer a phosphate from a donor nucleoside monophosphate to an acceptor nucleoside, preferably inosine, deoxyinosine and guanosine. Has the highest activities for IMP and GMP followed by dIMP, dGMP and XMP. Could also catalyze the transfer of phosphates from pyrimidine monophosphates but with lower efficiency. Through these activities regulates the purine nucleoside/nucleotide pools within the cell.

Subunit / interactions. Homotetramer.

Subcellular location. Cytoplasm. Cytosol.

Tissue specificity. Widely expressed.

Disease relevance. Spastic paraplegia 45, autosomal recessive (SPG45) [MIM:613162] A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. Some SPG45 patients manifest intellectual disability, contractures and learning disability. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Allosterically activated by various compounds including ATP, 2,3-BPG/2,3-Bisphosphoglyceric acid and Ap4A/P1,P4-bis(5’-adenosyl) tetraphosphate. Binding of an allosteric activator is a prerequisiste to magnesium and substrate binding. Inhibited by inorganic phosphate.

Cofactor. Binds 1 Mg(2+) ion per subunit.

Similarity. Belongs to the 5’(3’)-deoxyribonucleotidase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P49902-1	1	yes
P49902-2	2

RefSeq proteins (31): NP_001127845, NP_001338098, NP_001338099, NP_001338100, NP_001338101, NP_001338102, NP_001338103, NP_001338104, NP_001338105, NP_001338106, NP_001338107, NP_001338108, NP_001338109, NP_001338110, NP_001338111, NP_001338112, NP_001338113, NP_001338114, NP_001338115, NP_001338116, NP_001338117, NP_001338118, NP_001338119, NP_001338120, NP_001338121, NP_001338122, NP_001338123, NP_001338124, NP_001338125, NP_001338126, NP_036361 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008380	HAD-SF_hydro_IG_5-nucl	Family
IPR016695	Pur_nucleotidase	Family
IPR023214	HAD_sf	Homologous_superfamily
IPR036412	HAD-like_sf	Homologous_superfamily

Pfam: PF05761

Enzyme classification (BRENDA):

• EC 3.1.3.5 — 5’-nucleotidase (BRENDA: 107 organisms, 375 substrates, 402 inhibitors, 307 Km, 66 kcat entries)

Substrate kinetics (BRENDA)

39 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
5’-AMP	0.0003–23	73
5’-IMP	0.0071–18	49
5’-GMP	0.0064–7.2	29
5’-UMP	0.014–56	27
5’-CMP	0.002–100	19
INOSINE	0.25–10.2	13
5’-DAMP	0.012–35	9
AMP	0.0091–1.49	8
5’-DGMP	0.044–142	7
4-NITROPHENYL PHOSPHATE	0.224–21.78	6
5’-DCMP	0.023–0.75	6
DCMP	0.012–0.193	6
5’-TMP	0.008–0.73	5
5’-XMP	0.065–2.9	5
5’-DTMP	0.008–22	4

Catalyzed reactions (Rhea), 12 shown:

• a ribonucleoside 5’-phosphate + H2O = a ribonucleoside + phosphate (RHEA:12484)
• a 2’-deoxyribonucleoside + a ribonucleoside 5’-phosphate = a ribonucleoside + a 2’-deoxyribonucleoside 5’-phosphate (RHEA:19961)
• GMP + H2O = guanosine + phosphate (RHEA:27714)
• IMP + H2O = inosine + phosphate (RHEA:27718)
• XMP + H2O = xanthosine + phosphate (RHEA:28530)
• dGMP + H2O = 2’-deoxyguanosine + phosphate (RHEA:29379)
• dIMP + H2O = 2’-deoxyinosine + phosphate (RHEA:29383)
• dIMP + inosine = 2’-deoxyinosine + IMP (RHEA:69572)
• dGMP + inosine = 2’-deoxyguanosine + IMP (RHEA:69580)
• inosine + GMP = guanosine + IMP (RHEA:69584)
• inosine + UMP = uridine + IMP (RHEA:69588)
• inosine + CMP = cytidine + IMP (RHEA:69592)

UniProt features (111 total): binding site 38, helix 29, strand 22, turn 7, modified residue 4, sequence variant 3, region of interest 2, active site 2, chain 1, compositionally biased region 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

43 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
2JC9	X-RAY DIFFRACTION	1.5
5L50	X-RAY DIFFRACTION	1.64
5OPM	X-RAY DIFFRACTION	1.68
5OPP	X-RAY DIFFRACTION	1.7
5OPK	X-RAY DIFFRACTION	1.74
5OPN	X-RAY DIFFRACTION	1.77
5K7Y	X-RAY DIFFRACTION	1.79
5OPL	X-RAY DIFFRACTION	1.8
6DDY	X-RAY DIFFRACTION	1.8
5L4Z	X-RAY DIFFRACTION	1.84
2XCW	X-RAY DIFFRACTION	1.9
6DDZ	X-RAY DIFFRACTION	1.97
6DD3	X-RAY DIFFRACTION	1.98
2XJC	X-RAY DIFFRACTION	2
2XJD	X-RAY DIFFRACTION	2
5OPO	X-RAY DIFFRACTION	2
6DE0	X-RAY DIFFRACTION	2.05
2XJF	X-RAY DIFFRACTION	2.1
6DE2	X-RAY DIFFRACTION	2.1
2JCM	X-RAY DIFFRACTION	2.15
6DE1	X-RAY DIFFRACTION	2.15
2J2C	X-RAY DIFFRACTION	2.2
6FIW	X-RAY DIFFRACTION	2.2
6DDL	X-RAY DIFFRACTION	2.26
2XCV	X-RAY DIFFRACTION	2.3
2XCX	X-RAY DIFFRACTION	2.3
2XJB	X-RAY DIFFRACTION	2.3
2XJE	X-RAY DIFFRACTION	2.3
6FIS	X-RAY DIFFRACTION	2.3
6FXH	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49902-F1	88.81	0.76

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 52 (nucleophile); 54 (proton donor)

Ligand- & substrate-binding residues (38): 54; 54; 144; 144; 144; 154; 154; 154; 154; 202; 202; 206 …

Post-translational modifications (4): 418, 502, 511, 527

Mutagenesis-validated functional residues (1):

Position	Phenotype
52	loss of 5’ nucleotidase activity.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-2161541	Abacavir metabolism
R-HSA-74259	Purine catabolism
R-HSA-9755088	Ribavirin ADME
R-HSA-1430728	Metabolism
R-HSA-15869	Metabolism of nucleotides
R-HSA-2161522	Abacavir ADME
R-HSA-8956319	Nucleotide catabolism
R-HSA-9748784	Drug ADME

MSigDB gene sets: 268 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GSE45365_NK_CELL_VS_CD8A_DC_UP, JI_RESPONSE_TO_FSH_UP, GOBP_REGULATION_OF_DEFENSE_RESPONSE_TO_VIRUS, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, HEIDENBLAD_AMPLICON_8Q24_DN, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_DEFENSE_RESPONSE_TO_VIRUS, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_NEGATIVE_REGULATION_OF_DEFENSE_RESPONSE, GOBP_ORGANOPHOSPHATE_CATABOLIC_PROCESS

GO Biological Process (14): allantoin metabolic process (GO:0000255), obsolete GMP catabolic process to guanine (GO:0006202), IMP catabolic process (GO:0006204), obsolete amide catabolic process (GO:0043605), GMP metabolic process (GO:0046037), IMP metabolic process (GO:0046040), dGMP metabolic process (GO:0046054), dGMP catabolic process (GO:0046055), adenosine metabolic process (GO:0046085), negative regulation of defense response to virus by host (GO:0050689), protein K48-linked ubiquitination (GO:0070936), nucleotide metabolic process (GO:0009117), GMP catabolic process (GO:0046038), antiviral innate immune response (GO:0140374)

GO Molecular Function (11): ATP binding (GO:0005524), 5’-nucleotidase activity (GO:0008253), identical protein binding (GO:0042802), metal ion binding (GO:0046872), nucleoside phosphotransferase activity (GO:0050146), ubiquitin protein ligase activity (GO:0061630), nucleotide binding (GO:0000166), catalytic activity (GO:0003824), protein binding (GO:0005515), transferase activity (GO:0016740), hydrolase activity (GO:0016787)

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Drug ADME	2
Abacavir ADME	1
Nucleotide catabolism	1
Metabolism	1
Metabolism of nucleotides	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
purine ribonucleotide catabolic process	2
purine ribonucleoside monophosphate catabolic process	2
purine ribonucleotide metabolic process	2
purine ribonucleoside monophosphate metabolic process	2
catalytic activity	2
cellular anatomical structure	2
metabolic process	1
IMP metabolic process	1
purine deoxyribonucleotide metabolic process	1
purine deoxyribonucleoside monophosphate metabolic process	1
purine deoxyribonucleotide catabolic process	1
purine deoxyribonucleoside monophosphate catabolic process	1
dGMP metabolic process	1
purine ribonucleoside metabolic process	1
negative regulation of defense response to virus	1
regulation of defense response to virus by host	1
protein polyubiquitination	1
nucleoside phosphate metabolic process	1
GMP metabolic process	1
innate immune response	1
defense response to virus	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleotidase activity	1
protein binding	1
cation binding	1
phosphotransferase activity, alcohol group as acceptor	1
nucleobase-containing compound kinase activity	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
binding	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1308 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NT5C2	CNNM2	Q9H8M5	790
NT5C2	NT5C1A	Q9BXI3	692
NT5C2	DCK	P27707	688
NT5C2	NT5C	Q8TCD5	654
NT5C2	NT5C3A	Q9H0P0	623
NT5C2	POM121L2	Q96KW2	618
NT5C2	AS3MT	Q9HBK9	618
NT5C2	PRPS1	P09329	615
NT5C2	PRPS1L1	P21108	601
NT5C2	NT5M	Q9NPB1	600
NT5C2	BORCS7	Q96B45	580
NT5C2	SLC29A1	Q99808	577
NT5C2	AMPD2	Q01433	569
NT5C2	CSMD1	Q96PZ7	568
NT5C2	TRIM26	Q12899	565

IntAct

70 interactions, top by confidence:

A	B	Type	Score
NT5C2	NME7	psi-mi:“MI:0915”(physical association)	0.670
NME7	NT5C2	psi-mi:“MI:0915”(physical association)	0.670
NT5C2	MOB3B	psi-mi:“MI:0915”(physical association)	0.620
NT5C2	NUDT18	psi-mi:“MI:0915”(physical association)	0.620
NT5C2	FXR2	psi-mi:“MI:0915”(physical association)	0.620
FXR2	NT5C2	psi-mi:“MI:0915”(physical association)	0.620
SNX15	NT5C2	psi-mi:“MI:0915”(physical association)	0.590
NT5C2	SDCBP	psi-mi:“MI:0915”(physical association)	0.560
ATP5PO	NT5C2	psi-mi:“MI:0915”(physical association)	0.560
NT5C2	MOB3C	psi-mi:“MI:0915”(physical association)	0.560
MOB1B	NT5C2	psi-mi:“MI:0915”(physical association)	0.560
SDCBP	NT5C2	psi-mi:“MI:0915”(physical association)	0.560
NT5C2	ATP5PO	psi-mi:“MI:0915”(physical association)	0.560
NT5C2	FAA2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (135): NT5C2 (Two-hybrid), NT5C2 (Two-hybrid), NT5C2 (Two-hybrid), NME7 (Two-hybrid), MOB1B (Two-hybrid), MOB3C (Two-hybrid), NT5C2 (Affinity Capture-MS), NUDT18 (Two-hybrid), NME7 (Two-hybrid), NT5C2 (Two-hybrid), NT5C2 (Two-hybrid), MOB3B (Two-hybrid), NOC4L (Two-hybrid), PTGES3 (Co-fractionation), NT5C2 (Affinity Capture-MS)

ESM2 similar proteins: A6QLK2, A6QNT8, D3ZMY7, D4A055, F1QH17, O00305, O35431, O95486, O95487, P40692, P49902, P54288, P56223, P97679, Q01973, Q0VGM9, Q13330, Q16514, Q1RMS5, Q3SWT1, Q3T174, Q3U2P1, Q3UNW5, Q3V1L4, Q5EBF1, Q5PYH5, Q5RA22, Q5RB16, Q5RE34, Q5RJZ1, Q5ZIZ4, Q61187, Q62599, Q6AY57, Q6DKB0, Q6H1L8, Q6IRE4, Q7ZWU5, Q80W47, Q80YA3

Diamond homologs: D3ZMY7, O46411, P49902, Q3V1L4, Q54XC1, Q5EBF1, Q5RA22, Q5ZIZ4, Q6DKB0, Q86YG4, A4IHT9, Q6GN91, Q75K12, Q6Q0N3, Q9H857

SIGNOR signaling

0 interactions.

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

This gene, when mutated to be over-active, has been linked to chemotherapy resistance in relapsed T-cell Acute Lymphoblastic Leukemia.

Clinical variants and AI predictions

ClinVar

260 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	19
Likely pathogenic	7
Uncertain significance	74
Likely benign	96
Benign	39

Top pathogenic / likely-pathogenic (26)

Variant ID	HGVS	Classification
100904	NM_001351169.2(NT5C2):c.85C>T (p.Arg29Ter)	Pathogenic
100905	NM_001351169.2(NT5C2):c.1225del (p.Ser409fs)	Pathogenic
100906	NM_001351169.2(NT5C2):c.989-1G>T	Pathogenic
100907	NM_001351169.2(NT5C2):c.445A>T (p.Arg149Ter)	Pathogenic
100908	NM_001351169.2(NT5C2):c.175+1G>A	Pathogenic
1685994	NM_001351169.2(NT5C2):c.1403T>C (p.Leu468Pro)	Pathogenic
1705923	NM_001351169.2(NT5C2):c.629del (p.Tyr210fs)	Pathogenic
1981323	NM_001351169.2(NT5C2):c.1109del (p.Leu370fs)	Pathogenic
2009302	NM_001351169.2(NT5C2):c.675T>G (p.Tyr225Ter)	Pathogenic
2147372	NM_001351169.2(NT5C2):c.595C>T (p.Gln199Ter)	Pathogenic
2413847	NM_001351169.2(NT5C2):c.1153_1154del (p.Lys385fs)	Pathogenic
2729444	NM_001351169.2(NT5C2):c.226del (p.Arg76fs)	Pathogenic
3024463	NM_001351169.2(NT5C2):c.1159+2T>G	Pathogenic
3706302	NM_001351169.2(NT5C2):c.115C>T (p.Arg39Ter)	Pathogenic
375572	NM_001351169.2(NT5C2):c.771+573_814-298del	Pathogenic
4699797	NM_001351169.2(NT5C2):c.516dup (p.Thr173fs)	Pathogenic
4717088	NC_000010.11:g.103091621_103091622insCCATCCTGGCTAACAAGGTGAAACCCCGTCTCTACTAAAAATACAAAAAATTAGCCGGGCGCGGTGGCGGGCNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAGAAAAGTGCTAGTT	Pathogenic
810633	NM_001351169.2(NT5C2):c.430C>T (p.Arg144Ter)	Pathogenic
952332	NM_001351169.2(NT5C2):c.1371T>A (p.Tyr457Ter)	Pathogenic
1029182	NM_001351169.2(NT5C2):c.539+1G>T	Likely pathogenic
1709433	NM_001351169.2(NT5C2):c.771+1G>A	Likely pathogenic
3024462	NM_001351169.2(NT5C2):c.1106T>C (p.Phe369Ser)	Likely pathogenic
3064786	NM_001351169.2(NT5C2):c.176-2A>G	Likely pathogenic
432907	NM_001351169.2(NT5C2):c.503TAG[1] (p.Val169del)	Likely pathogenic
563771	GRCh37/hg19 10q24.32-24.33(chr10:103891057-105339973)x1	Likely pathogenic
579655	NM_001351169.2(NT5C2):c.1272+1G>C	Likely pathogenic

SpliceAI

3272 predictions. Top by Δscore:

Variant	Effect	Δscore
10:103089904:GGCAT:G	acceptor_gain	1.0000
10:103089905:GCAT:G	acceptor_gain	1.0000
10:103089905:GCATC:G	acceptor_loss	1.0000
10:103089906:CAT:C	acceptor_gain	1.0000
10:103089906:CATC:C	acceptor_gain	1.0000
10:103089907:AT:A	acceptor_gain	1.0000
10:103089908:TC:T	acceptor_loss	1.0000
10:103089909:C:CC	acceptor_gain	1.0000
10:103089910:T:A	acceptor_loss	1.0000
10:103090610:C:T	donor_loss	1.0000
10:103090784:CTTT:C	acceptor_gain	1.0000
10:103090785:TTT:T	acceptor_gain	1.0000
10:103090786:TT:T	acceptor_gain	1.0000
10:103090786:TTCTA:T	acceptor_loss	1.0000
10:103090788:C:CC	acceptor_gain	1.0000
10:103090788:CTAAA:C	acceptor_loss	1.0000
10:103090789:T:G	acceptor_loss	1.0000
10:103090794:C:CT	acceptor_gain	1.0000
10:103090900:ATTTC:A	donor_gain	1.0000
10:103090932:ATAC:A	donor_loss	1.0000
10:103090933:TA:T	donor_loss	1.0000
10:103090934:A:T	donor_loss	1.0000
10:103090935:C:CA	donor_loss	1.0000
10:103090992:GATGC:G	acceptor_gain	1.0000
10:103090994:TGC:T	acceptor_gain	1.0000
10:103090995:GC:G	acceptor_gain	1.0000
10:103090996:CC:C	acceptor_gain	1.0000
10:103090997:C:CA	acceptor_loss	1.0000
10:103090997:C:CC	acceptor_gain	1.0000
10:103091562:A:AC	donor_gain	1.0000

AlphaMissense

3726 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:103089899:C:T	E487K	1.000
10:103089902:G:C	H486D	1.000
10:103090629:G:C	F477L	1.000
10:103090629:G:T	F477L	1.000
10:103090630:A:G	F477S	1.000
10:103090631:A:G	F477L	1.000
10:103090687:G:T	A458D	1.000
10:103090708:G:T	A451D	1.000
10:103090710:A:C	F450L	1.000
10:103090710:A:T	F450L	1.000
10:103090711:A:C	F450C	1.000
10:103090711:A:G	F450S	1.000
10:103090712:A:G	F450L	1.000
10:103090717:G:A	T448I	1.000
10:103090729:C:T	G444D	1.000
10:103090735:C:G	R442P	1.000
10:103090736:G:T	R442S	1.000
10:103090743:G:C	S439R	1.000
10:103090743:G:T	S439R	1.000
10:103090745:T:G	S439R	1.000
10:103090747:C:A	G438V	1.000
10:103090747:C:T	G438E	1.000
10:103090748:C:G	G438R	1.000
10:103090748:C:T	G438R	1.000
10:103090769:C:G	D431H	1.000
10:103091600:A:G	L392P	1.000
10:103093154:A:G	W382R	1.000
10:103093154:A:T	W382R	1.000
10:103093162:A:G	L379P	1.000
10:103093166:C:T	E378K	1.000

dbSNP variants (sampled 300 via entrez): RS1000045954 (10:103141308 A>G), RS1000046602 (10:103183282 TA>T), RS1000061595 (10:103165196 G>A), RS1000094716 (10:103195271 A>C,T), RS1000121482 (10:103111430 A>T), RS1000165464 (10:103126049 A>T), RS1000171106 (10:103171556 C>T), RS1000317061 (10:103177615 G>A), RS1000317403 (10:103171672 A>G), RS1000321932 (10:103104026 G>T), RS1000369217 (10:103128199 C>T), RS1000460724 (10:103165791 C>A), RS1000462531 (10:103193488 T>A), RS1000487411 (10:103146242 T>C), RS1000536397 (10:103158747 G>A)

Disease associations

OMIM: gene MIM:600417 | disease phenotypes: MIM:613162, MIM:303350

GenCC curated gene-disease

Disease	Classification	Inheritance
complex hereditary spastic paraplegia	Definitive	Autosomal recessive
hereditary spastic paraplegia 45	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
complex hereditary spastic paraplegia	Definitive	AR

Mondo (5): hereditary spastic paraplegia 45 (MONDO:0013165), neurodevelopmental disorder (MONDO:0700092), hereditary spastic paraplegia (MONDO:0019064), microcephaly (MONDO:0001149), complex hereditary spastic paraplegia (MONDO:0015150)

Orphanet (2): Autosomal recessive spastic paraplegia type 45 (Orphanet:320396), Hereditary spastic paraplegia (Orphanet:685)

HPO phenotypes

33 total (30 of 33 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000486	Strabismus
HP:0000545	Myopia
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001258	Spastic paraplegia
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001347	Hyperreflexia
HP:0001371	Flexion contracture
HP:0001762	Talipes equinovarus
HP:0002059	Cerebral atrophy
HP:0002061	Lower limb spasticity
HP:0002064	Spastic gait
HP:0002079	Hypoplasia of the corpus callosum
HP:0003202	Skeletal muscle atrophy
HP:0003487	Babinski sign
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0005830	Flexion contracture of toe
HP:0006380	Knee flexion contracture
HP:0006466	Ankle flexion contracture
HP:0006989	Dysplastic corpus callosum
HP:0008936	Axial hypotonia
HP:0011448	Ankle clonus
HP:0011462	Young adult onset
HP:0011463	Childhood onset

GWAS associations

97 associations (top):

Study	Trait	p-value
GCST000395_3	Systolic blood pressure	7.000000e-24
GCST000998_10	Coronary heart disease	1.000000e-09
GCST001072_2	Blood pressure	4.000000e-17
GCST001074_8	Blood pressure	7.000000e-12
GCST001227_7	Systolic blood pressure	7.000000e-26
GCST001235_11	Blood pressure	8.000000e-11
GCST001236_21	Blood pressure	1.000000e-15
GCST001242_17	Schizophrenia	3.000000e-08
GCST001565_4	Schizophrenia	2.000000e-09
GCST001851_9	Schizophrenia	3.000000e-07
GCST001877_31	Autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia (combined)	1.000000e-08
GCST002149_2	Schizophrenia	4.000000e-13
GCST002167_2	Blood pressure	1.000000e-06
GCST002289_22	Coronary artery disease	1.000000e-06
GCST002290_15	Coronary artery disease or large artery stroke	2.000000e-08
GCST002461_5	Body mass index	4.000000e-08
GCST002539_4	Schizophrenia	6.000000e-19
GCST002783_442	Body mass index	2.000000e-09
GCST002783_518	Body mass index	8.000000e-09
GCST003116_37	Coronary artery disease	5.000000e-09
GCST003117_1	Myocardial infarction	8.000000e-08
GCST003151_2	White matter lesion progression	1.000000e-06
GCST003272_3	Systolic blood pressure	3.000000e-09
GCST003272_5	Systolic blood pressure	1.000000e-07
GCST003275_10	Mean arterial pressure	2.000000e-06
GCST003811_2	Response to citalopram or escitalopram and depression	2.000000e-06
GCST004257_3	Systolic blood pressure (long-term average)	4.000000e-15
GCST004279_29	Systolic blood pressure	5.000000e-11
GCST004495_66	BMI (adjusted for smoking behaviour)	5.000000e-06
GCST004495_67	BMI (adjusted for smoking behaviour)	5.000000e-07

EFO canonical traits (19, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0006340	mean arterial pressure
EFO:0004340	body mass index
EFO:0007746	white matter lesion progression measurement
EFO:0004318	smoking behavior
EFO:0007986	reticulocyte count
EFO:0009188	Red cell distribution width
EFO:0004344	birth weight
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0006527	smoking status measurement
EFO:0009270	heel bone mineral density
EFO:0007876	insomnia measurement
EFO:0008328	chronotype measurement
EFO:0007820	cognitive behavioural therapy
EFO:0004346	neuroimaging measurement
EFO:0000195	metabolic syndrome
EFO:0004527	mean corpuscular hemoglobin

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D065886	Neurodevelopmental Disorders	F03.625
D015419	Spastic Paraplegia, Hereditary	C10.500.300.820; C10.574.500.495.820; C10.668.829.800.300.820; C16.131.666.300.820; C16.320.400.375.820

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3708197 (SINGLE PROTEIN)

Clinical evidence (CIViC)

Drug × variant × indication: 14 predictive associations from 14 curated evidence items; also 4 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
NT5C2 R367Q	Mercaptopurine + Thioguanine	Childhood Acute Lymphocytic Leukemia	Resistance	CIViC C	EID7812
NT5C2 D407A	Thioguanine + Mercaptopurine	T-cell Acute Lymphoblastic Leukemia	Resistance	CIViC D	EID632
NT5C2 D407A	Nelarabine + Arabinosylguanine	T-cell Acute Lymphoblastic Leukemia	Resistance	CIViC D	EID635
NT5C2 K359Q	Mercaptopurine + Thioguanine	T-cell Acute Lymphoblastic Leukemia	Resistance	CIViC D	EID631
NT5C2 K359Q	Arabinosylguanine + Nelarabine	T-cell Acute Lymphoblastic Leukemia	Resistance	CIViC D	EID636
NT5C2 R238W	Mercaptopurine + Thioguanine	Childhood Acute Lymphocytic Leukemia	Resistance	CIViC D	EID7813
NT5C2 R238W	Cytarabine + Gemcitabine + Doxorubicin + Prednisolone	Childhood Acute Lymphocytic Leukemia	Resistance	CIViC D	EID7816
NT5C2 R238W	Mercaptopurine + Thioguanine	B-lymphoblastic Leukemia/lymphoma	Resistance	CIViC D	EID8077
NT5C2 R367Q	Mercaptopurine + Thioguanine	T-cell Acute Lymphoblastic Leukemia	Resistance	CIViC D	EID630
NT5C2 R367Q	Nelarabine + Arabinosylguanine	T-cell Acute Lymphoblastic Leukemia	Resistance	CIViC D	EID633
NT5C2 R367Q	Cytarabine + Gemcitabine + Prednisolone + Doxorubicin	Childhood Acute Lymphocytic Leukemia	Resistance	CIViC D	EID7815
NT5C2 R367Q	Thioguanine + Mercaptopurine	Childhood Acute Lymphocytic Leukemia	Resistance	CIViC D	EID7862
NT5C2 S445F	Mercaptopurine + Thioguanine	Childhood Acute Lymphocytic Leukemia	Resistance	CIViC D	EID7814
NT5C2 S445F	Cytarabine + Doxorubicin + Gemcitabine + Prednisolone	Childhood Acute Lymphocytic Leukemia	Resistance	CIViC D	EID7817

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

3 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11191561	Toxicity	3	didanosine	HIV infectious disease
rs11598702	Toxicity	3	didanosine	HIV infectious disease
rs11598702	Metabolism/PK	3	gemcitabine	Neoplasms

PharmGKB variants

5 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11191561	NT5C2	3	2.25	1	didanosine
rs11598702	NT5C2	3	2.25	2	didanosine;gemcitabine
rs10883841	NT5C2		0.00	0
rs3740387	CNNM2, NT5C2		0.00	0
rs72846714	NT5C2		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Adenosine turnover

CTD chemical–gene interactions

47 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
bisphenol A	increases expression	2
methacrylaldehyde	increases expression, increases abundance, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Acrolein	affects cotreatment, increases expression, increases abundance	2
Air Pollutants	affects cotreatment, increases abundance, increases expression, decreases expression	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Ozone	affects cotreatment, increases expression, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Valproic Acid	affects expression, increases expression	2
Cyclosporine	increases expression, decreases expression	2
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
beta-lapachone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1
LDN 193189	affects cotreatment, increases expression	1
Bortezomib	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1
Amphotericin B	increases expression	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Cisplatin	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3750425	Binding	Inhibition of recombinant N-terminal truncated human cytosolic 5’-nucleotidase-2 assessed as inhibition of inosine 5’-monophosphate hydrolysis at 1 mM by rapid green malachite assay	Identification of Noncompetitive Inhibitors of Cytosolic 5’-Nucleotidase II Using a Fragment-Based Approach. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A5BU	HKiG2	Transformed cell line	Female
CVCL_A5BV	Hki-8	Transformed cell line	Female

Clinical trials (associated diseases)

269 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT07542548	PHASE4	COMPLETED	D-Cycloserine for Serine Palmitoyltransferase Inhibition
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT03961906	PHASE2	COMPLETED	Physiotherapy in Hereditary Spastic Paraplegia
NCT04768166	PHASE2	COMPLETED	Testing Miglustat Administration in Subjects With Spastic Paraplegia 11
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT06117020	PHASE1	COMPLETED	Single and Multiple Ascending Dose Study of MTR-601 in Healthy Individuals
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase